Asthma is a common, complex disease with both genetic and environmental influences whose prevalence is increasing worldwide. Identification of genes increasing susceptibility to asthma would have far-reaching public health impact from enhancing motivation to make behavioral and lifestyle changes in susceptible individuals to providing basic biological and clinical information about the development and treatment of asthma. Although extensive efforts have been undertaken to identify asthma-predisposing genes, the actual genes leading to this increased risk and to a basic understanding of asthma remain obscure. We have completed a genome screen for asthma and asthma-related phenotypes using 389 microsatellite markers in 365 families collected by the Genetics of Asthma International Network (GAIN) study, a collaborative study involving multiple clinical investigative sites, GlaxoSmithKline and the Duke Center for Human Genetics. We have identified a region on chromosome 8 that will be the focus of our investigations. We propose to perform follow-up genotyping of microsatellite markers in these regions in the original set of families and in an additional set of 651 famihes. Candidate genes in those regions will be analyzedusing linkage and family-based association. Our efforts in identifying new markers, SNPs and candidate genes for the follow-up studies will be aided by bioinformatics analyses and tools. In addition, we will develop a novel cohort of African-American asthmatic children and selected relatives, along with age-matched controls, to augment the GAIN series and allow generalizability of results to African-Americans, a racial group with a high prevalence of asthma. This new African-American series will be evaluated for relevant candidate genes, and it will also be relevant for investigations of gene-environment interactions. We believe that a detailed study of genetic factors and gene-environment interactions is an essential step to identifying targeted preventive strategies and more effective treatments.